Efficacy and safety of dolutegravir plus emtricitabine versus standard ART for the maintenance of HIV-1 suppression: 48-week results of the factorial, randomized, non-inferiority SIMPL’HIV trial. PLoS Medicine
Sculier et al. aimed to assess the 48-week efficacy and safety of dolutegravir (DTG) + emtrictabine (FTC) dual maintenance therapy in virologically suppressed people living with HIV (PWHIV) compared with standard combination antiretroviral therapy (cART).
Participants were enrolled between 12 May 2017 and 30 May 2018. Patients virologically suppressed for at least 24 weeks on standard cART were randomized 1:1 to switching to DTG + FTC or to continuing cART. The primary endpoint was the proportion of patients virologically suppressed with <100 copies/ml through 48 weeks; the secondary endpoints included virological suppression at 48 weeks according to the US Food and Drug Administration (FDA) snapshot analysis. Quality of life was evaluated using the PROQOL-HIV questionnaire.
Median nadir CD4 count was 246 cells/mm3; median age was 48 years; 17% of participants were female. DTG + FTC was non-inferior to cART. The proportion of patients with viral suppression (<100 copies/ml) through 48 weeks was 93.5% in the DTG + FTC arm and 94.7% in the cART arm in the intention-to-treat population (risk difference -1.2%; 95% CI −7.8% to 5.6%). Per-protocol analysis showed similar results, with viral suppression in 96.5% of patients in both arms (risk difference 0.0%; 95% CI -5.6% to 5.5%). Using the FDA snapshot algorithm, 84/93 (90.3%) participants in the DTG + FTC arm had an HIV-1 RNA viral load of <50 copies/ml compared to 86/94 (91.5%) participants on standard cART (risk difference -1.1%; 95% CI -9.3% to 7.1%; p = 0.791). Quality of life improved more between baseline and week 48 in the DTG + FTC compared to the cART arm (adjusted difference +2.6; 95% CI +0.4 to +4.7). There was no occurrence of resistance, and thus no loss of future drug options, among patients who virologically failed according to the primary or secondary outcome.
In conclusion, this study provides evidence that the combination of DTG + FTC expands the possibility of offering 2-drug simplification in maintenance treatment. The combination demonstrated non-inferiority in efficacy and safety, as well as a greater improvement in quality of life over time compared to standard regimens. An ongoing assessment of data from the SIMPL’HIV study regarding healthcare-related costs and patient choices and satisfaction will provide additional insights into potential advantages of dual therapy and patient-centered monitoring.
comment Huldrych Günthard und Dominique Braun
Congratulations on the publication of this truly important study conducted in the framework of the Swiss HIV Cohort Study. This study was carried out as part of a newly started program of the Swiss National Science Foundation aiming to push the conduction of investigator-initiated randomised clinical studies. Thanks to the tireless efforts of the study team in Geneva and all SHCS centers, this study has now been successfully published and adds important data to the field of dual regimens as well as other innovative outcomes.